Cells isolated from murine bone marrow (BM) can be driven to become smooth muscle progenitor cells (SPC) that express smooth muscle-specific (SM) markers at levels equivalent to those found in primary aortic SM cell cultures. SM alpha-actin, SM22-alpha and SM-MHC mRNA expression was 2386, 312 and 1.2-fold greater than BM at 10d, and 5143, 573, and 13.8-fold greater than BM at 21d, respectively. The presence of 50ng/mL PDGF-BB reversibly lowered SM marker mRNA and protein expression. Compared to fibrillar collagen (fCol), SPCs cultured on non-fibrillar collagen (mCol) exhibited 2.8-fold decreased SM alpha-actin expression by 72h, 5.3-fold increased apoptosis, and 4.3-fold decreased proliferation by 72h. SPCs on mCol were spindle-shaped, with disorganized cytoskeletal elements, whereas SPCs on fCol were flattened and polygonal with a mature cytoskeleton in a stress-fibre orientation. These results suggest that accumulation of PDGF-BB and non-fibrillar collagen in diseased vasculature may negatively affect the regenerative potential of SPCs.